tbuckley/cabot-search huggingface dataset:
Abstract P5-02-08: Biomarker associated with response to CDK4/6 inhibitors in metastatic hormone receptor positive breast cancer
Authors: Agnieszka Witkiewicz
Journal: Cancer Research (2023)

Abstract Background: In spite of widespread use and known mechanism of action, predictive biomarkers for the use of CDK4/6 inhibitors in conjunction with endocrine therapy have yet to emerge. Here a cohort of patients treated with standard-of-care combination regimens was utilized to explore features of disease and determinants of progression-free survival (PFS). Patients and Methods: In this cohort of 235 patients, &amp;gt;90% of patients were treated with Palbociclib in combination with either an aromatase inhibitor (AI) or fulvestrant (FUL). The PFS mirrored that observed in randomized clinical trials. A total of 151 patient tumor tissues were used for targeted gene expression analyses with the HTG-Oncology Biomarker Panel. The association of disease state and gene expression analyses were interrogated for disease evolution and association with PFS. Results: HER2 immunohistochemistry (HER20, Her21+, Her22+) was not associated with PFS in full cohort, or AI and FUL subgroup analyses. The lack of progesterone receptor (PR+, PR-), was associated with shorter PFS in the full patient cohort (p=0.012) and selectively in patients treated with AI (p=0.005), but not FUL. Gene expression-based subtyping indicated that the majority of patients, as expected, had luminal breast cancer; however, the predominant subtypes changed with treatment and disease evolution. Primary tissue from tumor resection was dominated by luminal A subtype, which diminished in the context of metastatic disease, and was rare in post-progression specimens. The luminal B, HER2, and basal subtypes exhibited shorter PFS in CDK4/6 inhibitor combinations (AI, p=0.01; FUL, p=0.03). Existing clinically developed breast cancer signatures (e.g. breast cancer index) had variable associations with PFS; however, high expression of gene signatures associated with cell cycle were broadly associated with short PFS. Concordantly, utilizing unbiased analyses, gene expression programs linked to cell cycle were associated with short PFS, while interferon response processes were associated with longer PFS. Algorithms that incorporated standard pathological and clinical variables with the gene expression data were developed that exhibited potent predictive power. Conclusions: Tumor evolution occurs on treatment with CDK4/6 inhibitors; however, analyses of pretreatment biopsies can inform the duration of PFS. These data support discrete biological processes associated with sensitivity/resistance. Predictive algorithms could be developed to inform features of treatment decision which will require prospective validation which is ongoing. Citation Format: Agnieszka Witkiewicz. Biomarker associated with response to CDK4/6 inhibitors in metastatic hormone receptor positive breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-02-08.
Abstract P5-12-07: Polygenic Risk Score in a cohort of 105 Breast Cancer patients previously tested with a multi gene panel for hereditary cancer
Authors: Nikolaos Tsoulos, Konstantinos Agiannitopoulos, Helen Goga, Theodoros Troupis, Christos Markopoulos
Journal: Cancer Research (2023)

Abstract AIM: Most patients tested by a 44-gene panel for hereditary cancer (HerediGene), even though they had a strong family history, have a negative result or a finding in a low-risk gene. This creates a question about the risk for these individuals to develop breast cancer. The Polygenic Risk Score is a tool used to identify and calculate the lifetime risk of developing breast cancer and thus we are investigating whether it can be used in our cohort of patients to identify this risk. PATIENTS AND METHODS: Among 111 patients analyzed with a 44-gene hereditary cancer panel, we were able to produce the Polygenic Risk Score for 105 of them. All the patients were diagnosed with breast cancer, and they all had a strong family history. We analyzed the ability of the PRS to identify the risk of the patients in combination with the findings of the 44-gene panel. RESULTS: Overall, 74% of patients with a family history had a negative PRS (with a cut-off of 20%). Among the BRCA positive patients all of them had a positive PRS and among all the high-risk gene positive cases, 70% had a positive PRS. On the other hand, among the low-risk genes and the negative cases 18.5% had a positive PRS. There is a positive correlation between the findings from the NGS panel analysis and the PRS. CONCLUSION: Our analysis shows that PRS is correlated to the findings of the 44-gene NGS panel having the majority of the PRS positive patients carry high risk mutations. In addition to this, in 18.5% of the patients with low-risk findings or negative result from the 44-gene panel, the PRS was positive which can explain the outcome of the patient since breast cancer had developed. This is an indication that the combination of PRS with the findings from the 44-gene panel can identify individuals with a higher risk of developing breast cancer. Citation Format: Nikolaos Tsoulos, Konstantinos Agiannitopoulos, Helen Goga, Theodoros Troupis, Christos Markopoulos. Polygenic Risk Score in a cohort of 105 Breast Cancer patients previously tested with a multi gene panel for hereditary cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-12-07.
Abstract P3-03-23: Breast Cancer and Subsequent Risk of Type 2 Diabetes Mellitus: A systematic review and Meta-Analysis
Authors: Nanna Jordt, Kasper Kjærgaard, Signe Borgquist, Reimar W. Thomsen, Deirdre Cronin-Fenton
Journal: Cancer Research (2023)

Abstract Introduction Due to improvements in breast cancer (BC) diagnostics and treatment, the population of BC survivors is growing. BC treatments may have adverse effects that lead to an increased risk of developing type 2 diabetes mellitus (T2D). It is therefore important to investigate the risk of T2D in patients with BC in general and according to type of adjuvant BC treatment. Objectives To conduct a systematic review and meta-analysis investigating the association between early BC and the risk of subsequent T2D diagnosis. A secondary aim was to examine this association according to type of adjuvant BC treatment––chemotherapy and endocrine therapy (ET). Methods We searched PubMed and Embase using variations of the search terms breast cancer (population), ET, tamoxifen, aromatase inhibitors (AIs) and chemotherapy (exposures), and diabetes mellitus (outcome). Two authors screened papers for eligibility by title and abstract using Covidence and reviewed full texts of eligible papers. Guided by the Meta-analysis of Observational Studies in Epidemiology (MOOSE) checklist, study data were extracted. Using random-effects models, we calculated relative risks (RRs) and associated 95% confidence intervals (CIs) for the association between BC, adjuvant BC treatment (ET overall, tamoxifen, and AIs), and subsequent T2D. We used funnel plots to assess publication bias in the analyses. Results Among 16 eligible studies, 11 reported on T2D risk after BC, chemotherapy, or ET; five studies investigated more than one association. Compared with patients without BC, those with BC had elevated risk of T2D overall (RR=1.27, 95%CI=1.15-1.41), particularly those who received any ET (RR=1.23, 95% CI=1.16-1.32). Among BC patients only, risk of T2D was higher for those who received tamoxifen compared with those who did not receive tamoxifen (RR=1.19, 95% CI=1.13-1.25). Due to few studies, analyses investigating T2D risk after treatment with AIs and chemotherapy were inconclusive. Conclusion Our findings support an association between BC and subsequently elevated risk of T2D, particularly after tamoxifen use. Further research is needed to determine the impact of ET overall, AIs and chemotherapy on the incidence of T2D in patients with early BC. Funding This project was funded from the following source: The Novo Nordisk Foundation (NNF20OC0065928) Citation Format: Nanna Jordt, Kasper Kjærgaard, Signe Borgquist, Reimar W. Thomsen, Deirdre Cronin-Fenton. Breast Cancer and Subsequent Risk of Type 2 Diabetes Mellitus: A systematic review and Meta-Analysis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-03-23.
Abstract P5-08-15: Reducing Rates of Chronic Breast Cancer Related Lymphedema with Screening &amp; Early Intervention: An Update of Recent Data
Authors: Pat Whitworth, Frank Vicini, Stephanie Valente, Kirstyn Brownson, Beth Dupree, Manpreet Kohli, Laura Lawson, Chirag Shah
Journal: Cancer Research (2023)

Abstract Background: Breast cancer related lymphedema (BCRL) represents a dreaded complication of breast cancer treatment that can lead to morbidity, diminished quality of life, and psychosocial harm and is associated with increased costs. Increasingly, data has supported the concept of prospective BCRL surveillance coupled with early intervention to mitigate these effects. Methods: We performed a systematic review of the literature searching for published randomized and prospective data evaluating prospective BCRL surveillance with early intervention. Results: We identified 12 studies (2,907 patients) including 4 randomized trials (1,203 patients) and 8 prospective studies (1,704 patients). Randomized data consistently demonstrate that early intervention reduces rates of progression to chronic BCRL with multiple paradigms and diagnostic modalities utilized; the strongest data in the review comes from the randomized PREVENT trial which demonstrated early detection with bioimpedance spectroscopy (BIS), coupled with a compression garment applied for 12 hours a day over 4 weeks, significantly reduced the rate of chronic BCRL compared to tape measurement. Conclusions: Current data support the role of prospective BCRL surveillance with early detection and intervention to reduce rates of chronic BCRL. Breast cancer patients at risk for BCRL should undergo prospective surveillance as part of survivorship. Given the level 1 data demonstrating that BIS is superior to conventional tape measure, it should be included as the standard BCRL diagnostic modality unless an equally effective modality is employed. Citation Format: Pat Whitworth, Frank Vicini, Stephanie Valente, Kirstyn Brownson, Beth Dupree, Manpreet Kohli, Laura Lawson, Chirag Shah. Reducing Rates of Chronic Breast Cancer Related Lymphedema with Screening &amp; Early Intervention: An Update of Recent Data [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-08-15.
Abstract P2-23-09: Ultra-high Tumor Mutation Burden in Metastatic/Clinically Advanced Breast Cancer (MBC)
Authors: Kristina Fanucci, maryam lustberg, Neal Fischbach, Maureen Pelletier, Abirami Sivapiragasam, Prashanth Ashok Kumar, Mansi Kallem, Natalie A. Danziger, Ethan Sokol, Smruthy Sivakumar, Dean Pavlick, Jeffrey S. Ross, Lajos Pusztai
Journal: Cancer Research (2023)

Abstract Background: High (HTMB) tumor mutation burden (TMB) defined as ≥10 mutations/megabase (Mb) identifies breast cancer patients who could benefit from pembrolizumab. The higher the TMB the greater the likelihood of benefit. The goal of this analysis was to determine the frequency and genomic landscape of MBC with ultra-high TMB (UHTMB) defined as a TMB &amp;gt; 20 mutations/Mb. Design 2,049 MBC patients (pts) underwent hybrid capture based comprehensive genomic profiling for genomic alterations (GA) in at least 324 genes including determination of TMB to guide therapy decisions using the FoundationOne®CDx assay. ER, PR and HER2 expression were abstracted from submitted pathology reports. Results: 165 of 2049 MBC (8.1%) had HTMB &amp;gt; 10 mutations/Mb, among these 45 (2.2% of all cases) had UHTMB. When compared with the 2,004 non-UHTMB MBC pts with TMB &amp;lt; 20 mutations/Mb, the 45 UHTMB pts were older (mean 64.6 yrs vs 58.2 yrs; p&amp;lt;.0001), more often had lobular histology (40.00% vs 14.5%; p&amp;lt;.0001) and ER+ disease (86.6% vs 70.0%), had higher average driver GA/tumor (9.84 vs 5.7; p&amp;lt;.0001), and less often had TNBC (13.3% vs 27.0%; p=.041) compared to non-UHTMB high cancers. There were no significant differences in ancestry. Mutation signature analysis revealed that APOBEC was predominant in UHTMB samples (82.5%) with a minor portion with an MMR signature (10%), however, MSI-H status was significantly higher in UHTMB high cases (11.6% vs 0.40%; p&amp;lt;.0001). GA more frequently identified in UHTMB cases included CDH1 (45.50% vs 14.32%; p&amp;lt;.0001), PIK3CA (81.80% vs 37.86%; p&amp;lt;.0001), CDKN2A (11.40% vs 3.19%; p=.017), ARID1A (25.00% vs 5.01%; p&amp;lt;.0001) and NF1 (20.50% vs 5.94%; p=.0014). PD-L1 (CD274) gene amplification (2.3% vs 1.3%) or protein expression by the Ventana SP142 assay (57.14% vs 51.10%) were not significantly different. Conclusions: UHTMB MBC is a rare but clinically important subset in breast cancer that could have high response rates to single agent pembrolizumab. This phenotype is driven by APOBEC mutagenesis, more often seen in ER+ lobular cancers, and have higher frequencies of MSI-high status and mutations in CDH1 and PIK3CA. Citation Format: Kristina Fanucci, maryam lustberg, Neal Fischbach, Maureen Pelletier, Abirami Sivapiragasam, Prashanth Ashok Kumar, Mansi Kallem, Natalie A. Danziger, Ethan Sokol, Smruthy Sivakumar, Dean Pavlick, Jeffrey S. Ross, Lajos Pusztai. Ultra-high Tumor Mutation Burden in Metastatic/Clinically Advanced Breast Cancer (MBC) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-23-09.
Abstract P6-05-60: People with metastatic breast cancer face barriers to finding information and support
Authors: Robin H. Pugh-Yi, Piri Welcsh, Kelly Owens, Diane Rose, Erica Kuhn, Craig T. Dearfield, Susan Friedman
Journal: Cancer Research (2023)

Abstract People with metastatic breast cancer face barriers to finding information and support Background FORCE, a national nonprofit organization developed a health communication tool to help patients assess research relevance, key findings, and the quality of media reporting on cancer to support informed and shared health decision-making. People with metastatic breast cancer (mBC) are a priority population. Methods The organization conducted a survey about awareness of and access to breast cancer information and supportive services for people living with metastatic breast cancer. The organization promoted the survey through e-mail and social media, and a network of partner organizations that serve the metastatic breast cancer community. The survey invited respondents to volunteer to participate in focus groups and a follow-up survey in order to support efforts to serve this priority population. Results and Conclusions While interest in clinical trials was high, many users reported that thy do not know how to find an appropriate clinical trial. A majority of the 335 respondents were interested in information about clinical trials, treatment side effects, research findings, long-term health issues, diet/exercise, fatigue, and emotional health. Three quarters of the respondents indicated that they had never participated in a clinical trial, 67% indicated they would be interested in participating in the future, and about 40% indicated they did not know how to find a clinical trial recruiting people with metastatic breast cancer. Approximately one-third of participants were unable to obtain referrals to services they sought. Other barriers to services included lack of insurance coverage, lack of availability, and the COVID-19 public health emergency. Focus group responses indicate that women with mBC find the health communication tool to be useful, and appropriate in language, images, and tone. Results indicate that women with mBC are interested in finding information about clinical trials and other topics related to treatment side effects and quality of life. FORCE and partners are incorporating these results into tailored online resources to meet the needs of the mBC community. Citation Format: Robin H. Pugh-Yi, Piri Welcsh, Kelly Owens, Diane Rose, Erica Kuhn, Craig T. Dearfield, Susan Friedman. People with metastatic breast cancer face barriers to finding information and support [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-05-60.
Abstract P6-08-14: Breast Cancer Treatment Choices and Results in Hispanic Women Without Funding for Radiation
Authors: Maria De Los Leon-Camarena, Neha Reddy, Kimberly Ellison, Boone Goodgame
Journal: Cancer Research (2023)

Abstract Background: Although the survival rates for breast cancer have improved, there is still a disparity gap between Hispanic women and non-Hispanic women. Hispanic women in the US are vulnerable to cancer inequalities due to a plethora of barriers including disproportionate poverty, lack of health insurance, and citizenship status. A Surveillance, Epidemiology, and End Results analysis found that Hispanic women had lower rates of both early-stage breast cancer and receipts of radiation therapy (RT) after breast-conserving surgery than White women. For patients without private or government health insurance, charity and county indigent programs have variable levels of coverage, and some patients cannot access radiation services. The aim of this study is to identify disparities in breast cancer treatment for patients referred to the Travis County indigent cancer treatment program. Methods: We analyzed new referrals to the Ascension Seton Breast Clinic from April 2020 to January 2022. Demographics, disease stage, funding and treatments were extracted from medical records. We compared funding status at the time of referral vs time of surgery. We also analyzed the type of surgery elected and if RT was indicated and received. Results: We found that out of 242 referrals, 116 were diagnosed with a new malignancy. Of the 116, a total of 76 underwent breast surgery and RT was considered in 64 of these patients. 61% received RT. Of the remaining 25 patients, 16 patients elected simple mastectomies and 9 did not have funding to cover radiation (income was not low enough to qualify for RT benefit under the health district). Of the 9 women who did not have funding about 78% identified as Hispanic or Latino. 4 opted for simple mastectomies thus no longer needing RT, 3 received modified radical mastectomies without RT, 1 accessed charity funding for RT and 1 had lumpectomy without radiation and had recurrence of her breast cancer. Overall, the rate of breast conserving surgery was 43%. Discussion: The safety net system for patients in the US without access to private or government funding for healthcare is inherently limited. Costs of radiation treatment for cancer can be prohibitive for charity and indigent programs, but patients are forced to choose between mastectomy or risk a higher rate of recurrence. This data will be used to advocate for health district funding for this patient population. Citation Format: Maria De Los Leon-Camarena, Neha Reddy, Kimberly Ellison, Boone Goodgame. Breast Cancer Treatment Choices and Results in Hispanic Women Without Funding for Radiation [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-08-14.
Abstract P4-07-57: Outcomes of Triple-Negative Breast Cancer In Older Versus Younger Women
Authors: Asma Munir, Saira Khawaja, Sohail Khan, Yousuf Sharaiha, Anita M. Huws
Journal: Cancer Research (2023)

Abstract Background: Triple-negative breast cancer (TNBC) is an aggressive disease characterized by lack of targeted therapy; main-stay of treatment being limited to surgery and chemotherapy. Older patients with TNBC are often underrepresented in the clinical trials, due to competing mortality risks. This study aims to assess the treatment and outcomes of triple negative breast cancer (TNBC) in older women relative to younger women. Methods: This was a retrospective cohort study of patients who presented with primary TNBC, age 34-94 years; stage I-III from Jan 1, 2013 to Dec 31, 2015. Patients’ demographics, clinical characteristics, treatment and outcomes were retrieved from the CANISC Register and individual patient (N=88). Breast cancer-specific survival (BCSS) was estimated by using Kaplan–Meier method, and adjusted for age, tumor size, tumor grade, nodal status and chemotherapy, using SPSS-19. Results: Fifty-one patients were less than 70 years old (57.9%) and 37 were 70 years and older (42.1%). There was no difference in the stage at presentation (stage I: 43% vs. 35%; stage 2: 49% vs. 49%; stage 3: 8% vs. 11%; P=.061). Older patients were less often treated with adjuvant chemotherapy (75% vs. 24%; P&amp;lt; 0.001). Mean follow-up was 48 months. Five-year BCSS was significantly poor for older patients (54% vs. 75%, P=.032). 5-year overall survival was also significantly worse for patients who did not receive adjuvant chemotherapy (50% vs. 88% P =0&amp;lt; 021). Conclusions: Overall survival in triple negative breast cancer is much worse in older women as compared to younger women and there is a significant benefit with adjuvant chemotherapy. Citation Format: Asma Munir, Saira Khawaja, Sohail Khan, Yousuf Sharaiha, Anita M. Huws. Outcomes of Triple-Negative Breast Cancer In Older Versus Younger Women [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-57.